Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 1, January-February, p. 35–42

Publication type: original article

Language: English

The Association Between the p53/ topoisomerase I and p53/ topoisomerase IIα Immunophenotypes and the Progression of Ovarian Carcinomas

Zależność między p53/topoizomerazą I i p53/topoizomerazą IIα immunofenotypem a progresją raka jajnika

Julia K. Bar1,, Piotr Grelewski1,, Leszek Noga2,, Jerzy Rabczyński3,, Marian Gryboś4,, Michał Jeleń1,

1 Department of Pathomorphology and Clinical Cytology, Wroclaw Medical University, Poland

2 Department of Pathophysiology, Wroclaw Medical University, Poland

3 Department of Pathomorphology, Wroclaw Medical University, Poland

4 First Department of Gynecology, Wroclaw Medical University, Poland

Abstract

Background. In in vitro studies it has been revealed that p53 protein expression might regulate topoisomerase I (topo I) and topoisomerase IIα (topo IIα) levels in tumor cells. So far, the association between the p53 protein and topo I and topo IIα expression and its impact on ovarian carcinoma progression has not been analyzed.
Objectives. The aim of the study was to examine the association between topo I and topo IIα expression and p53 protein overexpression with respect to the morphological features and progressive growth of ovarian tumors.
Material and Methods. The expression of the studied biomarkers was estimated by immunohistochemical staining in tumor sections from 136 malignant and 30 benign ovarian neoplasms.
Results. Significant differences for topo I, topo IIα and p53 expression between malignant and benign tumors were observed (p < 0.01). The expression of topo IIα and p53 protein was associated with advanced stages of ovarian carcinomas (p < 0.01). Differences between topo I-positive cases and low (G1) and high (G3) tumor grade had only borderline significance (p = 0.07). In ovarian carcinomas, positive correlations between topo I and topo IIα, topo I and p53 and topo IIα and p53 protein expression were revealed (p = 0.001). No relationship between the studied biomarkers was found in benign ovarian tumors (p > 0.05). p53/topo I and p53/topo IIα immunophenotypes were associated with advanced stages of ovarian carcinoma (p = 0.045 and p = 0.009, respectively). p53/topo IIα positive ovarian carcinomas were more frequently observed in high than in low tumor grades and the differences were only of borderline significance (p = 0.07).
Conclusion. Current findings suggest that on the one hand, cooperation between topo I, topo IIα and p53 protein participates in the progressive growth of ovarian tumors. On the other hand, simultaneous expression of the studied proteins identifies the subgroup of ovarian cancers with aggressive biological features which might be considered in therapy.

Streszczenie

Wprowadzenie. Badania in vitro wykazały, że białko p53 reguluje stężenie topoizomerazy I (topo I) i topoizomerazy II (topo II) w komórkach nowotworowych. W rakach jajnika nie prowadzono analizy związków między topo I, topo IIα i białkiem p53, ani nie oceniano ich wpływu na progresywny wzrost nowotworów jajnika.
Cel pracy. Ocena zależności między występowaniem topoizomerazy I i topoizomerazy IIα oraz białka p53 w rakach jajnika z uwzględnieniem cech morfologicznych nowotworu i jego progresywnego wzrostu.
Materiał i metody. Obecność topo I i IIα oraz białka p53 oceniano w 136 rakach i 30 nowotworach łagodnych jajnika z użyciem przeciwciał monoklonalnych, stosując metodę immunohistochemiczną.
Wyniki. Wykazano statystycznie istotne różnice w występowaniu topo I, topo IIα i białka p53 między rakami a łagodnymi nowotworami jajnika (p < 0,01). Obecność topo IIα i białka p53 była związana z wyższym stadium zaawansowania raka jajnika (p < 0,01). Topo I była częściej obserwowana w rakach o dużym stopniu złośliwości (G3) aniżeli w rakach o małym stopniu złośliwości (G1). Wykazane różnice były na granicy statystycznej istotności (p = 0,07). Zanotowano związek między występowaniem topo I i topo IIα oraz p53 i topo I lub topo IIα w rakach jajnika (p = 0,001). Takich zależności nie stwierdzono w łagodnych nowotworach jajnika (p > 0,05). Stwierdzono, ze w zaawansowanych rakach jajnika dominuje immunofenotyp p53/topo I+ oraz p53/topo IIα+ (odpowiednio: p = 0,045; p = 0,009). Na granicy statystycznej istotności były różnice w występowaniu p53/topo IIα+ przypadków z uwzględnieniem stopnia złośliwości nowotworu (p = 0,07).
Wnioski. Wyniki wskazują, że kooperacja między analizowanymi białkami może mieć istotne znacznie w progresywnym wzroście nowotworów jajnika. Jednoczesne występowanie białka p53 i topo I lub p53 i topo IIα może charakteryzować podgrupę raków jajnika o agresywnych biologicznych cechach, które mogą być uwzględniane w terapii nowotworów tego narządu.

Key words

ovarian neoplasms, topoisomerases, p53 protein, progression, immunohistochemistry

Słowa kluczowe

nowotwory jajnika, topoizomerazy, białko p53, progresja, immunohistochemia

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